Postnatal neovascularization has been previously considered to result exclusively from the proliferation, migration, and remodeling of fully differentiated endothelial cells (ECs) derived from pre-existing blood vessels, i.e., angiogenesis. The formation of blood vessels from endothelial progenitor cells (EPCs)- i.e., vasculogenesis- has been considered restricted to embryogenesis. Preliminary studies recently completed in the investigator's laboratory suggest that under appropriate conditions, a subpopulation of CD34+ and/or Flk-1+ cells circulating in the peripheral blood can differentiate into ECs in vitro. Moreover, the investigators observed that such endothelial progenitor cells could incorporate into foci of ongoing neovascularization in rabbit and murine models of limb ischemia. When normal mice were lethally irradiated and transplanted with bone marrow (BM) harvested from transgenic mice, constitutively over- expression beta-galactosidase )beta-gal), the investigators observed incorporation of beta-gal-expressing BM-derived EPCs into foci of neovascularization in murine models of corneal injury, hind limb ischemia, myocardial infarction, and syngeneic colon cancer. These same models may be utilized to demonstrate that enhancement of circulating EPCs by exogenous administration or endogenous mobilization of EPCs may augment neovascularization. Preliminary data of the investigator thus challenge the conventional notion that postnatal vascularization is synonymous with angiogenesis. The experiments outlined in the proposal are designed to establish further evidence in this regard, clarify certain mechanisms and circumstance which may be responsible for modulating the contribution of vasculogenesis to postnatal neovascularization, and explore the possibility that modulation of vasculogenesis might be used therapeutically to augment as well as to inhibit neovascularization.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL060911-02
Application #
6030922
Study Section
Pathology A Study Section (PTHA)
Project Start
1998-07-01
Project End
2003-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
St. Elizabeth's Medical Center of Boston
Department
Type
DUNS #
073797292
City
Boston
State
MA
Country
United States
Zip Code
01235
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